Abstract

Autosomal Dominant Cerebellar Ataxia (ADCA) Type III is a type of spinocerebellar
ataxia (SCA) classically characterized by pure cerebellar ataxia and occasionally
by non-cerebellar signs such as pyramidal signs, ophthalmoplegia, and tremor. The
onset of symptoms typically occurs in adulthood; however, a minority of patients develop
clinical features in adolescence. The incidence of ADCA Type III is unknown. ADCA
Type III consists of six subtypes, SCA5, SCA6, SCA11, SCA26, SCA30, and SCA31. The
subtype SCA6 is the most common. These subtypes are associated with four causative
genes and two loci. The severity of symptoms and age of onset can vary between each
SCA subtype and even between families with the same subtype. SCA5 and SCA11 are caused
by specific gene mutations such as missense, inframe deletions, and frameshift insertions
or deletions. SCA6 is caused by trinucleotide CAG repeat expansions encoding large
uninterrupted glutamine tracts. SCA31 is caused by repeat expansions that fall outside
of the protein-coding region of the disease gene. Currently, there are no specific
gene mutations associated with SCA26 or SCA30, though there is a confirmed locus for
each subtype. This disease is mainly diagnosed via genetic testing; however, differential
diagnoses include pure cerebellar ataxia and non-cerebellar features in addition to
ataxia. Although not fatal, ADCA Type III may cause dysphagia and falls, which reduce
the quality of life of the patients and may in turn shorten the lifespan. The therapy
for ADCA Type III is supportive and includes occupational and speech modalities. There
is no cure for ADCA Type III, but a number of recent studies have highlighted novel
therapies, which bring hope for future curative treatments.